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GACVS June 2015 report 1 |
Global Advisory Committee on Vaccine Safety
(GACVS)
Report on GACVS meeting
June 2015
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GACVS June 2015 report 2 |
Vaccine Safety Net (VSN)
l Identify websites that provide useful, reliable information about vaccine safety and meet quality of content standards
l GACVS work group updated evaluation criteria
l 15000 visitors per year on WHO VSN homepage
l Currently 35 sites listed and 10 under evaluation – 10 languages – 16 countries
l Proposed upgrades – VSN logo – Create network of expertise – Survey of sites web metrics – Explore social networks and mobile device applications
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GACVS June 2015 report 3 |
Observed rates of adverse reactions
l WHO information on priority vaccines maintained since 2000 – Vaccine-specific information sheets developed in 2012 – Support WHO position papers – Describe known adverse reactions, with expected rates, and addresses major
AEFI
l Methodological review – Enhance systematic approach to literature review and evaluate quality of
evidence – Main challenge – Rare events and post-marketing assessment cannot be
addressed by randomized clinical trials – Need for alternative tools for assessing the quality of observational studies – GACVS work group will propose specific safety questions that warrant
systematic reviews (severe reactions and others of special interest) – Updated information sheets will be accompanied by summary tables, on the
model of position papers
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GACVS June 2015 report 4 |
Two candidate Ebola virus vaccines (data as at June 2015)
l ChAd3 EBO-Z – In clinical development since September 2014 – Phase 1 studies data available – Dose-ranging 10E10 to 10E11 viral particles per dose – Dose-related reactogenicity observed
• Injection-site pain • Fever within first 24 hours, resolving rapidly
– Transient decrease in lymphocytes and platelet counts – No serious adverse events documented
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GACVS June 2015 report 5 |
Two candidate Ebola virus vaccines (data as at June 2015)
l VSV-ZEBOV – In clinical development since October 2014 – Phase 1a/b studies data available – Dose-ranging 3x10E3 to 3x10E6 pfu per dose – Non-specific dose-related reactogenicity
• Injection-site pain • Systemic symptoms (fever, malaise, flu-like) within first 72 hours
– Viraemia (PCR) up to 2 weeks – Vaccine virus in saliva and urine in a few subjects – Arthralgia, arthritis, dermatitis, rash and cutaneous vasculitis at varying
frequency during 2nd week (more frequent with higher age) – Vaccine virus identified in joints and skin – Joint reaction not dose dependent, lasted for 2-3 weeks, some persistent – No serious adverse events documented
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GACVS June 2015 report 6 |
Two candidate Ebola virus vaccines VSV-ZEBOV update and GACVS conclusions
l Mid-August update with manufacturer in preparation for SAGE working group
– New study with higher titers up to 10E8 pfu per dose still blinded but only mild reactions and few systemic reactions
– Preliminary data among children aged 4 years and older with similar reactogenicity profile
– Data from phase 2/3 still limited to serious AEFI, none classified as vaccine related
l GACVS conclusions – Safey profile of both vaccines so far reassuring – Insufficient or no data for several important sub-groups (pregnancy,
lactation, chronic conditions, HIV infection, children) – Safety monitoring to continue for now under study conditions
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GACVS June 2015 report 7 |
Preparing for RTS,S introduction
l Two safety signals from Phase 3 trial discussed at December 2014 meeting
– Meningitis – Febrile convulsions (resolved with no sequelae)
l Meningitis signal – Various aetiologies, no temporal clustering – More frequent in 5-17 months cohort – Will require further assessment post Phase 3
l Data on HIV positive children – N=200, age 6-17 weeks – No other safety signal identified
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GACVS June 2015 report 8 |
Preparing for RTS,S introduction
l Malaria vaccine work group to develop guidance for post-licensure safety surveillance
l Adverse events of special interest require specific approaches tailored to local clinical settings
l Theoretical concern for auto-immune disorders (AID) related to use of new adjuvant
– No evidence or risk from experimental or human data – Numerous practical constraints for establishing AID surveillance (few cases
diagnosed in sub-Saharan Africa and epidemiology largely undetermined) à GACVS advises not to recommend monitoring for AID with possible revision if
new evidence becomes available (passive surveillance or use of the same adjuvant with other vaccines)
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GACVS June 2015 report 9 |
RTS,S and cerebral malaria
l Post-hoc analysis conducted after GACVS
l Excess number of cerebral malaria cases among RTS,S recipients compared to controls (p=0.03) in children first vaccinated at 5-17 months of age
– In first 20 months – In both vaccinated groups after booster – Higher CFR than other severe malaria cases – More cases in areas with high malaria transmission
l Very few cerebral malaria cases consistent with meningitis
l Cerebral malaria does not explain severe malaria rebound effect
à New signal identified that warrants further monitoring in post-licensure studies
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GACVS June 2015 report 10 |
CYD-TDV dengue vaccine
l Previously reviewed by GACVS in December 2012 and December 2014
l Long-term follow-up data presented (NEJM 2015;373:1195-206)
– Higher risk of hospitalized dengue among vaccine recipients aged 2-5 years in Asian study (RR=7.45, 95%CI 1.15-313.80)
– Protective effect among vaccine recipients aged > 9 years in Asian study (RR=0.57, 95%CI 0.18-1.86) and Latin American study (RR=0.53, 95%CI 0.25-1.16)
à Revised indication for administration at 9-60 years of age
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GACVS June 2015 report 11 |
CYD-TDV dengue vaccine
l GACVS recommendation – Importance of understanding potential factors associated with
increased risk among young children from Asian study – Assess if protective effect among older age groups is sustained over
time – Assess risk of dengue hospitalization over time among older subjects
who were serologically naive at the time of vaccination – Pursue follow-up of controlled trial in both regions – Need for additional information on co-administration with other age-
appropriate vaccines – Assess vaccine safety among pregnant women and immune-
compromised individuals – Generate additional safety data among older age groups (Phase 3
trials were conducted among subjects up to 16 years of age)
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GACVS June 2015 report 12 |
Topics for December 2015
l Vaccine safety signals in UMC data base
l Mass psychogenic reactions following vaccination
l HPV vaccines and autonomic disorders
l Update on narcolepsy and pandemic influenza vaccines
l Safety of smallpox vaccines